Differential effects of progestins on the circulating IGF-I system

Campagnoli, C; Abbà, Chiara; Ambroggio, Simona; Peris, Clementina

doi:10.1016/j.maturitas.2003.09.017

Cited by 25 publications

(31 citation statements)

References 29 publications

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“…Indeed, our serologic data were consistent with prior reports of changes in the IGF-axis related to the first-pass effect: total IGF-I, free IGF-I, and IGFBP-3 levels were highest among women not using hormone therapy, lowest among women using estrogen, and intermediate among women using estrogen + progesterone (reflecting the fact that progestins partially offset the estrogen effects; refs. 43,49). Insulin levels were also significantly lower in hormone therapy users in our data set, and a wide range of other factors may also be altered by the use of oral estrogen.…”

Section: Discussionmentioning

confidence: 54%

Insulin, Insulin-like Growth Factor-I, Endogenous Estradiol, and Risk of Colorectal Cancer in Postmenopausal Women

et al. 2008

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Obesity is a risk factor for colorectal cancer, and hyperinsulinemia, a common condition in obese patients, may underlie this relationship. Insulin, in addition to its metabolic effects, has promitotic and antiapoptotic activity that may be tumorigenic. Insulin-like growth factor (IGF)-I, a related hormone, shares sequence homology with insulin, and has even stronger mitogenic effects. However, few prospective colorectal cancer studies directly measured fasting insulin, and none evaluated free IGF-I, or endogenous estradiol, a potential cofactor in postmenopausal women. Therefore, we conducted a casecohort investigation of colorectal cancer among nondiabetic subjects enrolled in the Women's Health Initiative Observational Study, a prospective cohort of 93,676 postmenopausal women. Fasting baseline serum specimens from all incident colorectal cancer cases (n = 438) and a random subcohort (n = 816) of Women's Health Initiative Observational Study subjects were tested for insulin, glucose, total IGF-I, free IGF-I, IGF binding protein-3, and estradiol. Comparing extreme quartiles, insulin [hazard ratio (HR) q4-q1 , 1.73; 95% confidence interval (CI), 1.16-2.57; P trend = 0.005], waist circumference (HR q4-q1 , 1.82; 95% CI, 1.22-2.70; P trend = 0.001), and free IGF-I (HR q4-q1 , 1.35; 95% CI, 0.92-1.98; P trend = 0.05) were each associated with colorectal cancer incidence in multivariate models. However, these associations each became nonsignificant when adjusted for one another. Endogenous estradiol levels, in contrast, were positively associated with risk of colorectal cancer (HR comparing high versus low levels, 1.53; 95% CI, 1.05-2.22), even after control for insulin, free IGF-I, and waist circumference. These data suggest the existence of at least two independent biological pathways that are related to colorectal cancer: one that involves endogenous estradiol, and a second pathway broadly associated with obesity, hyperinsulinemia, and free IGF-I. [Cancer Res 2008;68(1):329-37]

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Section: Discussionmentioning

confidence: 54%

Insulin, Insulin-like Growth Factor-I, Endogenous Estradiol, and Risk of Colorectal Cancer in Postmenopausal Women

et al. 2008

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“…particular, dydrogesterone exhibits a very weak effect on the GH axis (25). Our study particularly pointed to the facilitative interaction of steroids and ghrelin pathway in driving GH secretion.…”

Section: Tablementioning

confidence: 55%

Estro-progestin supplementation enhances the growth hormone secretory responsiveness to ghrelin infusion in postmenopausal women

Villa¹,

Costantini²,

Perri³

et al. 2008

Fertility and Sterility

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“…First, oral hormone therapy may expose the liver to a large bolus of estrogen (the so-called first-pass effect), which could alter hepatic protein synthesis. It is known that oral estrogens result in decreased synthesis of insulin-IGF-I axis components (47,48), which are positively associated with the risk of colorectal cancer (6). Conversely, expression of sex hormonebinding globulin, the main estrogen-binding protein in circulation, is increased in hormone therapy users, leading to reduced levels of bioavailable estrogen (49).…”

Section: Discussionmentioning

confidence: 99%

Reproductive history and risk of colorectal cancer in postmenopausal women.

Zervoudakis¹,

Schatzkin²,

Strickler³

et al. 2010

JCO

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Colorectal cancer is the fourth most common cancer and the second leading cause of cancer death in the United States, with approximately 142 570 new cases and 51 370 colorectal cancer-related deaths expected in 2010 (1). Observational and experimental evidence suggest that sex hormones, particularly estrogen, play a role in colorectal cancer pathogenesis (2). Most notably, a substantial body of epidemiological data supports an inverse relationship between postmenopausal oral hormone therapy use and the risk of colorectal cancer (3), an association that was confirmed by results of the Women's Health Initiative (WHI) Clinical Trial, which reported a statistically significant decreased risk of colorectal cancer among women using estrogen plus progestin formulations (but not among women using estrogen alone) compared with women using placebo (4,5).By contrast, two subsequent prospective studies reported a positive association between endogenous estrogen level and the risk of colorectal cancer in postmenopausal women. The first investigation, which was conducted in the WHI Observational Study, found that a high endogenous level of estrogen was associated with a 1.5-fold increased risk of developing colorectal cancer after adjustment for established colorectal cancer risk factors (6). Similarly, the New York University Women's Health Study reported a 60% increased risk of colorectal cancer for women in the highest quartile of circulating estrogen level compared with those in the lowest quartile (7). The positive associations between endogenous estrogen level and the risk of colorectal cancer reported by these investigations are consistent with laboratory data demonstrating the proliferative effects of exogenous estradiol in colorectal tissue and in colorectal cancer cell lines (8-11). The findings from these observational and experimental studies, when considered together with the data on hormone therapy use and colorectal cancer, suggest that endogenous and exogenous sex hormones may play different roles in colorectal tumorigenesis.

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Differential effects of progestins on the circulating IGF-I system

Cited by 25 publications

References 29 publications

Insulin, Insulin-like Growth Factor-I, Endogenous Estradiol, and Risk of Colorectal Cancer in Postmenopausal Women

Insulin, Insulin-like Growth Factor-I, Endogenous Estradiol, and Risk of Colorectal Cancer in Postmenopausal Women

Estro-progestin supplementation enhances the growth hormone secretory responsiveness to ghrelin infusion in postmenopausal women

Reproductive history and risk of colorectal cancer in postmenopausal women.

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